Although non-insulin-dependent diabetes (NIDDM) is associated with increased risk for atherosclerotic cardiovascular disease (CVD), a major part of the excess risk is not explained by the diabetic state per se. Insulin resistance, an antecedent of NIDDM, has been found to be associated with several CVD risk factors including hypertension, hyperlipidemia, obesity, and hypercoagulability. The principal aim of the proposal is to test the hypothesis that insulin resistance is an independent risk factor and a precursor for CVD in a large multi-ethnic population. The specific aims are: 1) to determine if insulin resistance is associated with increased prevalence of CVD independent of obesity, glycemia, and insulinemia; 2) to determine the impact of insulin resistance on CVD risk factors including blood pressure, lipids, lipoproteins, and coagulation factors at different stages of glucose tolerance; 3) to investigate the ethnic differences in the relationship between insulin resistance and CVD; and 4) to establish the basis for a prospective study to determine if insulin resistance predicts the development of CVD and its risk factors. The study will be conducted at three different sites to include four different ethnic groups; non-Hispanic whites (Los Angeles and San Antonio), Blacks (Los Angeles), Mexican Americans (San Antonio), and Pima Indians (Phoenix). Four hundred men and women aged 40-69 years of each ethnic group will be included. They will be selected to cover the three categories of glucose tolerance (normal, impaired, and NIDDM). The following tests and procedures will be performed on each subject over two days. The first day will involve history taking (personal, family, general, medical, dietary, physical activity, and Rose questionnaire), physical examination, and non-invasive cardiovascular evaluation (electrocardiogram, Doppler of peripheral vessels. Duplex scanning of the carotids, and echocardiogram). Blood will be collected for measurement of fasting lipids, lipoproteins, coagulation factors, and glycated hemoglobin, and study of blood rheology (blood and plasma viscosity, and red blood cell aggregation) and an oral glucose tolerance test will be performed. The second day will be devoted to assessment of insulin resistance. The minimal model approach will be used as it is most suited to a large epidemiological study. In addition to being accurate and reproducible, it is easy to perform, safe, and cost-effective. In a subset of subjects, a third visit will be required to study insulin secretion and postprandial lipids and lipoprotein profile after a standardized meal test. The findings of this study are expected to determine the extent and the significance of the relation between insulin resistance and CVD at different stages of glucose tolerance among various ethnic groups which will have public health implications in planning future intervention strategies.